One-year changes in brain microstructure differentiate preclinical Huntington's disease stages.

OBJECTIVE: To determine whether brain imaging markers of tissue microstructure can detect the effect of disease progression across the preclinical stages of Huntington's disease. METHODS: Longitudinal microstructural changes in diffusion imaging metrics (mean diffusivity and fractional anisotropy) were investigated in participants with presymptomatic Huntington's disease (N = 35) stratified into three preclinical subgroups according to their estimated time until onset of symptoms, compared with age- and gender-matched healthy controls (N = 19) over a 1y period. RESULTS: Significant differences were found over the four groups in change of mean diffusivity in the posterior basal ganglia and the splenium of the corpus callosum. This overall effect was driven by significant differences between the group far-from-onset (FAR) of symptoms and the groups midway- (MID) and near-the-onset (NEAR) of symptoms. In particular, an initial decrease of mean diffusivity in the FAR group was followed by a subsequent increase in groups closer to onset of symptoms. The seemingly counter-intuitive decrease of mean diffusivity in the group furthest from onset of symptoms might be an early indicator of neuroinflammatory process preceding the neurodegenerative phase. In contrast, the only clinical measure that was able to capture a difference in 1y changes between the preclinical stages was the UHDRS confidence in motor score. CONCLUSIONS: With sensitivity to longitudinal changes in brain microstructure within and between preclinical stages, and potential differential response to distinct pathophysiological mechanisms, diffusion imaging is a promising state marker for monitoring treatment response and identifying the optimal therapeutic window of opportunity in preclinical Huntington's disease

Fixed points and amenability in non-positive curvature

Consider a proper cocompact CAT(0) space X. We give a complete algebraic characterisation of amenable groups of isometries of X. For amenable discrete subgroups, an even narrower description is derived, implying Q-linearity in the torsion-free case. We establish Levi decompositions for stabilisers of points at infinity of X, generalising the case of linear algebraic groups to Is(X). A geometric counterpart of this sheds light on the refined bordification of X (\`a la Karpelevich) and leads to a converse to the Adams-Ballmann theorem. It is further deduced that unimodular cocompact groups cannot fix any point at infinity except in the Euclidean factor; this fact is needed for the study of CAT(0) lattices. Various fixed point results are derived as illustrations.Comment: 33 page

Could Work Be a Source of Behavioural Disorders? A Study in Horses

Stress at work, as shown by a number of human studies, may lead to a variety of negative and durable effects, such as impaired psychological functioning (anxiety, depression…). Horses share with humans this characteristic of working on a daily basis and are submitted then to work stressors related to physical constraints and/or more “psychological” conflicts, such as potential controversial orders from the riders or the requirement to suppress emotions. On another hand, horses may perform abnormal repetitive behaviour (“stereotypies”) in response to adverse life conditions. In the present study, we investigated whether the type of work the horses are used for may have an impact on their tendency to show stereotypic behaviour (and its type) outside work. Observations in their box of 76 horses all living in the same conditions, belonging to one breed and one sex, revealed that the prevalence and types of stereotypies performed strongly depended upon the type of work they were used for. The stereotypies observed involved mostly mouth movements and head tossing/nodding. Work constraints probably added to unfavourable living conditions, favouring the emergence of chronic abnormal behaviours. This is especially remarkable as the 23 hours spent in the box were influenced by the one hour work performed every day. To our knowledge, this is the first evidence of potential effects of work stressors on the emergence of abnormal behaviours in an animal species. It raises an important line of thought on the chronic impact of the work situation on the daily life of individuals

Provider Attitudes toward the Voluntary Medical Male Circumcision Scale-Up in Kenya, South Africa, Tanzania and Zimbabwe.

Countries participating in voluntary medical male circumcision (VMMC) scale-up have adopted most of six elements of surgical efficiency, depending on national policy. However, effective implementation of these elements largely depends on providers' attitudes and subsequent compliance. We explored the concordance between recommended practices and providers' perceptions toward the VMMC efficiency elements, in part to inform review of national policies. As part of Systematic Monitoring of the VMMC Scale-up (SYMMACS), we conducted a survey of VMMC providers in Kenya, South Africa, Tanzania, and Zimbabwe. SYMMACS assessed providers' attitudes and perceptions toward these elements in 2011 and 2012. A restricted analysis using 2012 data to calculate unadjusted odds ratios and 95% confidence intervals for the country effect on each attitudinal outcome was done using logistic regression. As only two countries allow more than one cadre to perform the surgical procedure, odds ratios looking at country effect were adjusted for cadre effect for these two countries. Qualitative data from open-ended responses were used to triangulate with quantitative analyses. This analysis showed concordance between each country's policies and provider attitudes toward the efficiency elements. One exception was task-shifting, which is not authorized in South Africa or Zimbabwe; providers across all countries approved this practice. The decision to adopt efficiency elements is often based on national policies. The concordance between the policies of each country and provider attitudes bodes well for compliance and effective implementation. However, study findings suggest that there may be need to consult providers when developing national policies.\u

El Nino and Health Risks from Landscape Fire Emissions in Southeast Asia

Emissions from landscape fires affect both climate and air quality. Here, we combine satellite-derived fire estimates and atmospheric modelling to quantify health effects from fire emissions in southeast Asia from 1997 to 2006. This region has large interannual variability in fire activity owing to coupling between El Nino-induced droughts and anthropogenic land-use change. We show that during strong El Nino years, fires contribute up to 200 micrograms per cubic meter and 50 ppb in annual average fine particulate matter (PM2.5) and ozone surface concentrations near fire sources, respectively. This corresponds to a fire contribution of 200 additional days per year that exceed the World Health Organization 50 micrograms per cubic metre 24-hr PM(sub 2.5) interim target and an estimated 10,800 (6,800-14,300)-person (approximately 2 percent) annual increase in regional adult cardiovascular mortality. Our results indicate that reducing regional deforestation and degradation fires would improve public health along with widely established benefits from reducing carbon emissions, preserving biodiversity and maintaining ecosystem services

Uk Clinical Experience Up to 52 Weeks With Linaclotide for Irritable Bowel Syndrome With Constipation

BACKGROUND: Linaclotide, a guanylate cyclase C agonist, has been shown in clinical trials to improve symptoms of irritable bowel syndrome with constipation (IBS-C). Here we report data from a real-world study of linaclotide in the UK. METHODS: This 1-year, multicentre, prospective, observational study in the UK enrolled patients aged 18 years and over initiating linaclotide for IBS-C. The primary assessment was change from baseline in IBS Symptom Severity Scale (IBS-SSS) score at 12 weeks, assessed in patients with paired baseline and 12-week data. Change from baseline in IBS-SSS score at 52 weeks was a secondary assessment. Adverse events were recorded. RESULTS: In total, 202 patients were enrolled: 185 (91.6%) were female, median age was 44.9 years (range 18.1-77.2) and 84 (41.6%) reported baseline laxative use. Mean (standard deviation) baseline IBS-SSS score was 339 (92), with most patients (n = 129; 66.8%) classified as having severe disease (score ⩾300). In patients with paired data, there was a significant mean (95% confidence interval) decrease in IBS-SSS score from baseline to 12 weeks [-77.0 (-96.3, -57.7); p < 0.001; n = 124] and baseline to 52 weeks [-70.7 (-95.0, -46.5); p < 0.001; n = 76]. Overall, 174 adverse events were reported in 77 (38.1%) patients, most commonly diarrhoea (n = 54; 26.7%), abdominal pain (n = 21; 10.4%) and abdominal distension (n = 13; 6.4%). CONCLUSION: Linaclotide significantly improved IBS-SSS score at 12 and 52 weeks. These results provide insights into outcomes with linaclotide treatment over 1 year in patients with IBS-C in real-world clinical practice

Ethnobotanical study of some of mosquito repellent plants in north-eastern Tanzania

The use of plant repellents against nuisance biting insects is common and its potential for malaria vector control requires evaluation in areas with different level of malaria endemicity. The essential oils of Ocimum suave and Ocimum kilimandscharicum were evaluated against malaria vectors in north-eastern Tanzania. An ethnobotanical study was conducted at Moshi in Kilimanjaro region north-eastern Tanzania, through interviews, to investigate the range of species of plants used as insect repellents. Also, bioassays were used to evaluate the protective potential of selected plants extracts against mosquitoes. The plant species mostly used as repellent at night are: fresh or smoke of the leaves of O. suave and O. kilimandscharicum (Lamiaceae), Azadirachta indica (Meliaceae), Eucalyptus globules (Myrtaceae) and Lantana camara (Verbenaceae). The most popular repellents were O. kilimandscharicum (OK) and O. suave (OS) used by 67% out of 120 households interviewed. Bioassay of essential oils of the two Ocimum plants was compared with citronella and DEET to study the repellence and feeding inhibition of untreated and treated arms of volunteers. Using filter papers impregnated with Ocimum extracts, knockdown effects and mortality was investigated on malaria mosquito Anopheles arabiensis and Anopheles gambiae, including a nuisance mosquito, Culex quinquefasciatus. High biting protection (83% to 91%) and feeding inhibition (71.2% to 92.5%) was observed against three species of mosquitoes. Likewise the extracts of Ocimum plants induced KD90 of longer time in mosquitoes than citronella, a standard botanical repellent. Mortality induced by standard dosage of 30 mg/m2 on filter papers, scored after 24 hours was 47.3% for OK and 57% for OS, compared with 67.7% for citronella. The use of whole plants and their products as insect repellents is common among village communities of north-eastern Tanzania and the results indicate that the use of O. suave and O. kilimandscharicum as a repellent would be beneficial in reducing vector biting. The widespread use of this approach has a potential to complement other control measures

Morphometry Based on Effective and Accurate Correspondences of Localized Patterns (MEACOLP)

Local features in volumetric images have been used to identify correspondences of localized anatomical structures for brain morphometry. However, the correspondences are often sparse thus ineffective in reflecting the underlying structures, making it unreliable to evaluate specific morphological differences. This paper presents a morphometry method (MEACOLP) based on correspondences with improved effectiveness and accuracy. A novel two-level scale-invariant feature transform is used to enhance the detection repeatability of local features and to recall the correspondences that might be missed in previous studies. Template patterns whose correspondences could be commonly identified in each group are constructed to serve as the basis for morphometric analysis. A matching algorithm is developed to reduce the identification errors by comparing neighboring local features and rejecting unreliable matches. The two-sample t-test is finally adopted to analyze specific properties of the template patterns. Experiments are performed on the public OASIS database to clinically analyze brain images of Alzheimer's disease (AD) and normal controls (NC). MEACOLP automatically identifies known morphological differences between AD and NC brains, and characterizes the differences well as the scaling and translation of underlying structures. Most of the significant differences are identified in only a single hemisphere, indicating that AD-related structures are characterized by strong anatomical asymmetry. In addition, classification trials to differentiate AD subjects from NC confirm that the morphological differences are reliably related to the groups of interest